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Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):9731-9736. doi: 10.1073/pnas.1617876114. Epub 2017 Aug 21.

Insulin-like growth factor 1 receptor regulates hypothermia during calorie restriction.

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Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037.
School of Medicine and Psychology, Autonomous University of Baja California, Tijuana, BC, Mexico, 22390.
Biological Sciences Postdoctoral Program, National Autonomous University of Mexico, Mexico City, Mexico, 04510.
Department of Biological Sciences, University of California, San Diego, CA 92093.
Department of Neurochemistry, University of Stockholm, Stockholm, Sweden, 106 91.
INSERM, Saint-Antoine Research Center, Paris, France, 75012.
Pierre et Marie Curie Faculty of Medicine, Sorbonne University, Paris, France, 75012.
INSERM, Saint-Antoine Research Center, Paris, France, 75012;
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037;
Department of Neuroscience, The Scripps Research Institute, La Jolla, CA 92037.
Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037.


When food resources are scarce, endothermic animals can lower core body temperature (Tb). This phenomenon is believed to be part of an adaptive mechanism that may have evolved to conserve energy until more food becomes available. Here, we found in the mouse that the insulin-like growth factor 1 receptor (IGF-1R) controls this response in the central nervous system. Pharmacological or genetic inhibition of IGF-1R enhanced the reduction of temperature and of energy expenditure during calorie restriction. Full blockade of IGF-1R affected female and male mice similarly. In contrast, genetic IGF-1R dosage was effective only in females, where it also induced transient and estrus-specific hypothermia in animals fed ad libitum. These effects were regulated in the brain, as only central, not peripheral, pharmacological activation of IGF-1R prevented hypothermia during calorie restriction. Targeted IGF-1R knockout selectively in forebrain neurons revealed that IGF signaling also modulates calorie restriction-dependent Tb regulation in regions rostral of the canonical hypothalamic nuclei involved in controlling body temperature. In aggregate, these data identify central IGF-1R as a mediator of the integration of nutrient and temperature homeostasis. They also show that calorie restriction, IGF-1R signaling, and body temperature, three of the main regulators of metabolism, aging, and longevity, are components of the same pathway.


IGF-1R; aging; calorie restriction; energy homeostasis; temperature

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